Devices, methods, and applications for recirculation of fluids in microfluidic channels

Abstract

The present invention provides devices and methods for generating a pulsatile fluid flow in a microchannel by means of external actuation of a thin flexible film. With the devices described herein, cycles of positive and negative actuation can be used to infuse or withdrawal fluid in a microchannel. Fluid can be recirculated over one or more microfluidic feature, such as a chemical or molecular receptor, biosensor, electrode, cell or biological material, chromatography feature, mixer, etc., in a way that would represent an advantage over the single-pass flow techniques common to most microfluidic devices. The devices and methods are particularly useful in vitro diagnostics (IVD), analytical chemistry, chromatography, and mixing applications in a variety of fields.

What is claimed is: 
     
         1 . A fluid recirculating cartridge device, comprising:
 a cartridge body;   a central chamber embedded in the cartridge body;   at least one microchannel embedded in the cartridge body, the at least one microchannel being fluidly connected at a proximal end to the central chamber;   at least one sensor region embedded in the cartridge body, each of the at least one sensor region being positioned on a fluid path of the at least one microchannel;   a waste reservoir embedded in the cartridge body, the waste reservoir being fluidly connected to a distal end of the at least one microchannel; and   an actuating chamber embedded in the cartridge body, wherein the actuating chamber is fluidly connected to the waste reservoir and comprises an externally depressible flexible membrane.   
     
     
         2 . The device of  claim 1 , wherein the fluid connection between the proximal end of the at least one microchannel and the central chamber comprises a passive valve. 
     
     
         3 . The device of  claim 1 , wherein each of the at least one sensor region comprises an array of sensor spots, each sensor spot comprising at least one capture molecule or probe. 
     
     
         4 . The device of  claim 3 , wherein the capture molecule or probe is selected from the group consisting of: antibodies, antibody fragments, antigens, proteins, nucleic acids, oligonucleotides, peptides, lipids, lectins, inhibitors, activators, ligands, hormones, cytokines, sugars, amino acids, fatty acids, phenols, and alkaloids. 
     
     
         5 . The device of  claim 3 , wherein each sensor spot is about 100 μm in diameter and is arranged in a circular array with a pitch of about 200 μm and a diameter of about 3 mm. 
     
     
         6 . The device of  claim 1 , further comprising at least one hermetically sealed fluid chamber embedded in the cartridge body, wherein the seal of each fluid chamber is configured to be breakable to fluidly connect each fluid chamber to the central chamber by a microchannel. 
     
     
         7 . The device of  claim 6 , wherein each fluid chamber comprises a liquid selected from a wash buffer, water, or a reagent. 
     
     
         8 . The device of  claim 6 , further comprising a reagent chamber positioned on a fluid path between a fluid chamber and the central chamber. 
     
     
         9 . The device of  claim 8 , wherein the reagent chamber comprises a liquid or a solid-state reagent. 
     
     
         10 . The device of  claim 1 , wherein the central chamber is configured to receive a liquid sample. 
     
     
         11 . The device of  claim 10 , wherein the at least one microchannel is configured to draw the liquid sample towards the at least one sensor region by capillary action. 
     
     
         12 . The device of  claim 11 , wherein the actuating chamber is configured to recirculate the liquid sample over the at least one sensor region upon depressing and releasing the flexible membrane. 
     
     
         13 . The device of  claim 1 , wherein the cartridge body has a planar shape with a length between about 50 mm and 150 mm, a width between about 50 mm and 150 mm, and a thickness between about 1 mm and 10 mm. 
     
     
         14 . The device of  claim 13 , wherein the length is about 75 mm, the width is about 26 mm, and the thickness is about 1.6 mm. 
     
     
         15 . A cartridge reader device, comprising:
 an external housing;   a screen mounted on the external housing;   a cartridge port sized to receive the cartridge of  claim 1 ; and   an internal mount;   wherein the internal mount comprises at least one stepper motor and at least one optical sensor.   
     
     
         16 . The device of  claim 15 , wherein the cartridge port comprises lateral springs configured to align an inserted cartridge such that an actuating chamber of the cartridge is aligned with the at least one stepper motor and at least one sensor region of the cartridge is aligned with the at least one optical sensor. 
     
     
         17 . The device of  claim 16 , wherein the at least one stepper motor is configured to depress and release a flexible membrane of an aligned actuating chamber. 
     
     
         18 . The device of  claim 15 , wherein the internal mount further comprises at least one solenoid. 
     
     
         19 . The device of  claim 18 , wherein the cartridge port comprises lateral springs configured to align an inserted cartridge such that at least one fluid chamber is aligned with the at least one solenoid. 
     
     
         20 . The device of  claim 19 , wherein the at least one solenoid is configured to break a hermetic seal of the at least one fluid chamber. 
     
     
         21 . A method of recirculating fluids, comprising the steps of:
 dispensing a sample fluid such that it flows into a microchannel; and   performing at least one actuation of a membrane of a chamber fluidly connected to the microchannel;   wherein the at least one actuation of the membrane passes the sample fluid over at least one sensor region positioned in a fluid path of the microchannel.   
     
     
         22 . A squeeze bulb cartridge device, comprising:
 a cartridge body;   a microchannel embedded in the cartridge body, the at least one microchannel being fluidly connected at a proximal end to a squeezable bulb and at a distal end to a distal port; and   at least one sensor region embedded in the cartridge body, each of the at least one sensor region being positioned on a fluid path of the at least one microchannel;   wherein a length of the microchannel has a winding path forming a flow restrictor region configured to reduce a flow of fluid within the microchannel.